Differences in carrier frequency between mothers of Duchenne and Becker muscular dystrophy patients

Abstract

Duchenne and Becker muscular dystrophies (DMD/BMD) are X-linked inherited muscular disorders caused by mutations in the dystrophin gene. Two-thirds of DMD cases are thought to be caused by inheritance from carrier mothers and this study aimed to clarify and compare the carrier frequency of mothers of DMD and BMD patients according to the mutation type. We included 139 DMD and 19 BMD mothers. Of these, 113 patients (99 DMD and 14 BMD) and 13 patients (12 DMD and 1 BMD) had deletions and duplications of one or more exons, respectively. Small mutations, including nonsense mutations, small deletions/insertions and splice site mutations, were identified in 32 patients (28 DMD and four BMD). The overall carrier frequency for BMD mothers was significantly higher than for DMD (89.5% vs 57.6%, P<0.05), probably as BMD patients can leave descendants. The carrier frequency tended to be lower in mothers of DMD patients with deletion mutations than with duplications and small mutations (53.5%, 66.7% and 67.9%, respectively). It was suggested that de novo mutations are more prevalent for deletions than other mutations. This is the first report to analyze the carrier frequency according to mutation type.

Prenatal diagnosis of Duchenne muscular dystrophy and cytogenetic analysis in 303 Chinese families

“…This may because of the difference of enrolled population. Besides, the carrier rate of deletion mutations (47.4%) was much lower compared with the duplication rate (87.5%) among the mothers with mutations which is in accordance with previous study [29]. The identification of female carriers of DMD gene mutation is crucial to prevent the birth of DMD children.…”

Frequency of de novo mutations in Japanese patients with Fabry disease

“…The frequency of de novo mutations has been reported to be high in X-linked disorders such as Duchenne muscular dystrophy and hemophilia A and approximately one-third of mutations of these two diseases are expected to arise de novo [26], [27], [28]. The size and structure of the gene and its position within the genome may contribute to the frequency of the de novo mutations.…”

Empirical and Computational Comparison of Alternative Therapeutic Exon Skip Repairs for Duchenne Muscular Dystrophy

“…As expected, this 100 % culling of males results in a mutation-selection equilibrium in which one third of cases are de novo mutations, with the rest being created in female carriers in the prior few generations and little long term inheritance (GRIMM et al, 2012). However, for BMD-type edits this is not the case, with a much greater carrier incidence observed, ~ 90 %, (Lee et al, 2014) demonstrating that BMD alleles overall are under lower selection pressure, which should elevate their incidence relative to DMD. When examining the ratio of database incidence to this cross section, we find the opposite: the DMD type deletions, and one of our BMD-type edits are represented at a similar frequency, and two edits in particular seem underrepresented: Δe46-54 and Δe47-55.…”